Nonpenetrance of the most frequent autosomal recessive leber congenital amaurosis mutation in NMNAT1.

Autor:	Siemiatkowska AM; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands2Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands., Schuurs-Hoeijmakers JH; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands2Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands., Bosch DG; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands3Bartimeus Institute for the Visually Impaired, Zeist, the Netherlands., Boonstra FN; Bartimeus Institute for the Visually Impaired, Zeist, the Netherlands4Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands., Riemslag FC; Bartimeus Institute for the Visually Impaired, Zeist, the Netherlands5The Rotterdam Eye Hospital, Rotterdam, the Netherlands., Ruiter M; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands., de Vries BB; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands2Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands4Donders Institute for Brain, Cognition and Behavior, Rad., den Hollander AI; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands2Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands6Department of Ophthalmology, Radboud University Medical., Collin RW; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands2Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands., Cremers FP; Department of Human Genetics, Radboud University Medical Center, Nijmegen, the Netherlands2Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Jazyk:	angličtina
Zdroj:	JAMA ophthalmology [JAMA Ophthalmol] 2014 Aug; Vol. 132 (8), pp. 1002-4.
DOI:	10.1001/jamaophthalmol.2014.983
Abstrakt:	Importance: The NMNAT1 gene was recently found to be mutated in a subset of patients with Leber congenital amaurosis and macular atrophy. The most prevalent NMNAT1 variant was p.Glu257Lys, which was observed in 38 of 106 alleles (35.8%). On the basis of functional assays, it was deemed a severe variant. Observations: The p.Glu257Lys variant was 80-fold less frequent in a homozygous state in patients with Leber congenital amaurosis than predicted based on its heterozygosity frequency in the European American population. Moreover, we identified this variant in a homozygous state in a patient with no ocular abnormalities. Conclusions and Relevance: On the basis of these results, the p.Glu257Lys variant is considered not fully penetrant. Homozygotes of the p.Glu257Lys variant in most persons are therefore not associated with ocular disease. Consequently, genetic counselors should exercise great caution in the interpretation of this variant.
Databáze:	MEDLINE
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